title: Deep membrane insertion of prion protein upon reduction of disulfide bond.
abstract: The membrane may play a role in the pathogenesis of the prion protein (PrP). Cytoplasmic expression of PrP causes the conversion of PrP to a self-perpetuating PrP(Sc)-like conformation and the interaction of polypeptide chain with the hydrophobic core of the membrane is believed to be closely correlated with neurodegeneration. However, it is still elusive what factors govern the membrane interaction of PrP. Here, we show that PrP penetrates deeply into the membrane when the single disulfide bond is reduced, which results in membrane disruption and leakage. The proteinase K treatment and the fluorescence quenching assays showed that a predicted transmembrane domain of PrP penetrates into the membrane when the disulfide bond was reduced. Therefore, the oxidation state of PrP might be an important factor that influences its neurotoxicity or pathogenesis.
authors.affiliation: School of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Shin
authors.forename: Jae-Yoon
authors.initials: JY
authors.lastname: Shin
authors.forename: Jun-Seob
authors.initials: JS
authors.lastname: Kim
authors.forename: Yoo-Soo
authors.initials: YS
authors.lastname: Yang
authors.forename: Yeon-Kyun
authors.initials: YK
authors.lastname: Shin
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D006224:Cricetinae; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D019286:Endopeptidase K / Q000737:chemistry; D005453:Fluorescence; D047468:Immunoprecipitation; D010084:Oxidation-Reduction; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D004220:Disulfides; D018620:PrPSc Proteins; D053835:Unilamellar Liposomes; D019286:Endopeptidase K